T helper (TH) cells, key regulators of the immune system, are divided into two subsets, TH1 and TH2, based upon their pattern of cytokine synthesis (Paul and Seder (1994) Cell 76: 241–251). TH1 cells predominantly produce high levels of interleukin-2 (IL-2) and interferon-gamma (IFN-γ). TH1 cells also activate antigen-presenting cells (macrophages and dendritic cells) and enhance the cytotoxic activity of CD8+ Cytotoxic T-lymphocyte (CTL) and Natural Killer (NK) cells. In contrast, TH2 cells produce elevated levels of IL-4, IL-5 and IL-13, and mediate allergic responses as a result of inducing IgE isotype switching and differentiation of B cells into IgE secreting cells (De Vries and Punnonen (1996) In Cytokine regulation of humoral immunity: basic and clinical aspects. Eds. Snapper, C. M., John Wiley & Sons, Ltd., West Sussex, UK, p. 195–215).
It is desirable to modify the relative populations of TH1 and TH2 cells in various circumstances. Modulators which up-regulate TH1-mediated responses by, for example, directing the differentiation of naive T cells into TH1 cells, inducing TH1 cell proliferation, and increasing IFN-γ production and macrophage activation, are useful in promoting cell-mediated immunity to infectious agents such as bacterial, protozoan, intracellular parasitic and viral infections. Modulators which down-regulate TH1-mediated responses are useful in situations where a decreased cell-mediated immune response is desired, for example, in treatment of autoimmune diseases such as multiple sclerosis.
The discovery of novel cytokine polypeptides which modulate TH1-mediated responses, and nucleic acids encoding them, satisfies a need in the art by providing new compositions useful in modifying host immune responses and in treating disease.